Claims
- 1. A method for the preparation of a 2-azadihydroxybicyclo�2.2.1!heptane compound of formula: ##STR23## wherein * represents an R chirality, *' represents an S chirality, R is hydrogen or, respectively, a group of formula ##STR24## wherein R.sub.1 is alkyl and Ar is optionally substituted aryl, comprising bishydroxylating a bicyclo�2.2.1!heptene compound of formula ##STR25## in the presence of about 0.1 mol % to about 5 mol % of a metal osmate compound or about 0.06 mol % to about 0.07 mol % osmium tetroxide, and an oxidizing agent capable of regenerating osmium tetroxide.
- 2. The method according to claim 1 wherein R is the group of formula ##STR26##
- 3. The method according to claim 2 wherein R.sub.1 is methyl or ethyl, and Ar is optionally substituted phenyl, which when substituted is substituted by one or more methyl or methoxy.
- 4. The method according to claim 3 wherein R.sub.1 is methyl, and Ar is phenyl.
- 5. The method according to claim 1 wherein the bishydroxylation is effected using osmium tetroxide at about 0.06 mol % to about 0.07 mol %.
- 6. The method according to claim 5 wherein the osmium tetroxide is present at about 0.06 mol %.
- 7. The method according to claim 1 wherein the bishydroxylation is effected using metal osmate at about 0.1 mol % to about 5 mol %.
- 8. The method according to claim 7 wherein the metal osmate is present at about 0.2 to about 0.5 mol %.
- 9. The method according to claim 1 wherein the metal osmate is K.sub.2 OSO.sub.4.2H.sub.2 O.
- 10. The method according to claim 1 wherein the oxidizing agent capable of regenerating osmium tetroxide is N-methylmorpholine oxide.
- 11. A method for the preparation of an L-tartaric acid salt of the (1R) diastereomer of the 2-azadihydroxybicyclo�2.2.1!heptane compound according to claim 1, comprising treating the (1R) diastereomer of the 2-azadihydroxybicyclo�2.2.1!heptane compound according to claim 1 wherein R is a group of formula ##STR27## with L-tartaric acid.
- 12. The method according to claim 11 wherein R.sub.1 is methyl and Ar is phenyl.
- 13. The method according to claim 11 further comprising preparing the L-tartaric acid salt of the (1R) diastereomer of the 2-azadihydroxybicyclo�2.2.1 !heptane compound in a substantially enantiomerically purified state in the presence of a (1S) diastereomer of the 2-azadihydroxybicyclo�2.2.1!heptane compound.
- 14. The method according to claim 11 wherein the treating occurs in an aqueous-organic solvent mixture.
- 15. The method according to claim 14 wherein organic solvent is isopropanol.
- 16. The method according to claim 14 wherein the treating occurs in an aqueous-isopropanol solvent mixture having a volume ratio of about 30:70 to about 15:85.
- 17. The method according to claim 16 wherein the volume ratio is about 25:75.
Priority Claims (1)
Number |
Date |
Country |
Kind |
95-06353 |
May 1995 |
FRX |
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Parent Case Info
This application is a continuation-in-part of U.S. patent application Ser. No. 08/655,395, filed May 30, 1996, now allowed which in turn is a continuation-in-part of U.S. patent application Ser. No. 08/476,156, filed Jun. 7, 1995, now U.S. Pat. No. 5,631,383.
Non-Patent Literature Citations (2)
Entry |
Katagiri Muto Nomura Higashikawa Kaneko Synthesis of Carbocyclic Nucleosides from 2-Azabicyclo�2.2.1!hept -5-en-3-ones: Sodium BorohydrideMediated Carbon-Nitrogen Bond Chemical and Pharm. Bull., vol. 39, No. 5, 1991 (pgs. 1112-1122). |
Katagiri Muto Kaneko Stereospecific synthesis of Carbocyclic Nucleosides from 2-Azabicyclo�2.2.1!hept an-3-Ones Via Sodium Borohydride Mediated Tetrahedron Letters, vol. 30, No. 13, 1989, pp. 1645-1648. |
Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
655395 |
May 1996 |
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Parent |
476156 |
Jun 1995 |
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